Anaesthesiology

Is goal-directed haemodynamic therapy dead? No abstract available

Heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass BACKGROUND Heparin-associated coagulation disorder is an important factor related to postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Currently, the relationship between heparin sensitivity and postoperative bleeding is unknown. OBJECTIVE To investigate the relationship between individual heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery. DESIGN Prospective controlled study. SETTING Tertiary teaching hospital, Urumqi, Xinjiang, PR China. The study was conducted from January 2016 to August 2018. PATIENTS A total of 195 adult patients undergoing cardiac valve replacement surgery were included. INTERVENTION After initial heparin dosing (2.5 mg kg−1), patients were divided into three groups according to the whole blood activated clotting time (ACT): group A, insensitive group (ACT < 480 s); group B, sensitive group (480 s < ACT < 750 s); group C, hypersensitive group (ACT > 750 s). MAIN OUTCOME MEASURES First, intra-operative and 24-h postoperative blood loss. Second, antithrombin (AT) and factor X mRNA levels. Third, the plasma levels of AT-III and factor X. Fourth, heparin sensitivity index. RESULTS Blood loss was approximately 20 to 25% lower in group B than in groups A and C, which was statistically significant (P < 0.01). The AT-III mRNA levels increased from groups A to C and was positively associated with heparin sensitivity; the factor X mRNA levels changed in the opposite direction; a significant difference was observed between groups A and C (P < 0.05). The factor X plasma level showed the same trend as its mRNA. The AT-III plasma level was significantly lower in group B than in groups A and C (P < 0.05). CONCLUSION Postoperative blood loss is related to heparin sensitivity in patients undergoing cardiac surgery, and the moderately sensitive patients have the least postoperative bleeding. Individual variation in heparin sensitivity is related to the mRNA and plasma levels of AT-III and factor X. TRIAL REGISTRATION Registration number ChiCTR-RPC-17012259.

Fibrinolytic shutdown diagnosed with rotational thromboelastometry represents a moderate form of coagulopathy associated with transfusion requirement and mortality: A retrospective analysis BACKGROUND Viscoelastic techniques have made it possible to describe specific fibrinolytic phenotypes (physiological, hyperfibrinolysis and shutdown) and to establish a relationship of these phenotypes with outcome. However, there remains a debate as to whether shutdown is a state of hypercoagulability or rather a coagulopathy with moderate fibrinolysis and fibrinogen consumption. OBJECTIVES Our objectives were to describe the relationship between fibrinolytic phenotypes and outcomes, and to report the effects of tranexamic acid (TXA) administration. DESIGN This was a retrospective analysis of prospectively acquired data from a trauma registry. SETTING An academic level 1 trauma centre in the Lyon Region, from March 2011 to December 2016. PATIENTS We included all injured patients who had a rotational thromboelastometry analysis at admission. Fibrinolytic phenotypes were determined according to the maximum lysis: shutdown less than 3%, physiological 3 to 15%, hyperfibrinolysis more than 15%. MAIN OUTCOME MEASURE Mortality at 24 h and at hospital discharge. RESULTS During the study period, 473 patients were included with the following phenotypes: physiological (344 patients, 73%), shutdown (107 patients, 23%) and hyperfibrinolysis (22 patients, 5%). There was an increase in injury severity, prothrombin time ratio, fibrin degradation products and transfusion requirements from the physiological to the shutdown and hyperfibrinolysis phenotypes. Prehospital TXA administration increased the rate of shutdown and decreased the maximum lysis value at admission. After adjustment, multivariate analysis showed that fibrinolytic phenotypes, but not TXA, were independently associated with an increased risk of early death and death before hospital discharge: shutdown [odds ratio (95% confidence interval)] 2.4 (1.2 to 4.8) and hyperfibrinolysis 67.9 (7.4 to 624.2). CONCLUSION The results of the current study suggest that shutdown, which is associated with injury severity and mortality, probably reflects a moderate form of coagulopathy and fibrinolysis rather than a hypercoagulopathy. Therefore, the observation of shutdown fibrinolysis on thromboelastography/rotational thromboelastometry should not lead to withholding but rather to the administration of TXA.

Evaluation of autologous retransfusion from a closed suction drainage system for patient blood management in elective total hip and knee replacement: A two cohort study BACKGROUND Postoperative autologous retransfusion of drainage blood might reduce the transfusion of red blood cell concentrates after major orthopaedic surgery. OBJECTIVES Our primary objective was to evaluate the effectiveness of a blood collection and retransfusion system. Secondary objectives included safety issues and the quality of the drainage blood collected. DESIGN Combined retrospective and prospective cohort study. SETTING Swiss regional hospital, from 1 January to 31 December 2015 (retrospective cohort) and 1 January to 31 August 2018 (prospective cohort). PATIENTS The retrospective and prospective cohort included 216 and 46 patients, respectively, who underwent elective hip or knee replacement. INTERVENTIONS Use of a postoperative blood collection and retransfusion system. MAIN OUTCOME MEASURES The primary outcome was the postoperative haemoglobin in patients with and without autotransfusion. Secondary outcomes were percentage of patients with transfusion of allogeneic blood products and with adverse events with and without autotransfusion. Tertiary outcomes were laboratory levels of specific inflammation and coagulation parameters in collected drain blood directly after surgery and 6 h postoperatively. RESULTS Autologous retransfusion was performed in 50 patients (23%) in the retrospective analysis. Postoperative haemoglobin level was increased by 5 g dl−1 (P = 0.017) in retransfused patients compared with those without retransfusion. However, there was no difference in the number of transfused allogeneic red blood cell concentrates. Mild adverse transfusion reactions were reported in 13 retransfused patients (26%). Laboratory analyses for the second prospective part detected massively elevated concentrations of myeloperoxidase and IL-6 in the drainage blood, but C-reactive protein and procalcitonin concentrations were within normal ranges at both time points. D-dimers levels were above the upper normal level in 37 and 24% at the two time points, respectively, and tended to decrease over time (P = 0.060). CONCLUSION Our study questions the effectiveness of postoperative autotransfusion as part of a patient blood management programme. In addition, the obvious signs of inflammatory reactions and coagulation activation raise safety concerns. TRIAL REGISTRATION The cohort study was not registered in a trial registry.

Deep neuromuscular blockade during spinal surgery reduces intra-operative blood loss: A randomised clinical trial BACKGROUND Spinal surgery is usually performed in the prone position using a posterior approach. However, the prone position may cause venous engorgement in the back and thus increase surgical bleeding with interruption of surgery. The prone position also affects cardiac output since large vessels are compressed decreasing venous return to the heart. OBJECTIVE We hypothesised that deep neuromuscular blockade would be associated with less surgical bleeding during spinal surgery in the prone position. DESIGN Randomised, single blinded trial. SETTING University teaching hospital. PARTICIPANTS Eighty-eight patients in two groups. INTERVENTIONS Patients were randomly assigned to moderate neuromuscular blockade or deep neuromuscular blockade. In the moderate neuromuscular blockade group, administration of rocuronium was adjusted such that the train-of-four count was one to two. In the deep neuromuscular blockade group, rocuronium administration was adjusted such that the train-of-four count was zero with a posttetanic count 2 or less. MAIN OUTCOME MEASURES The primary outcome was the volume of intra-operative surgical bleeding. The surgeon's satisfaction with operating conditions, haemodynamic and respiratory status, and postoperative pain scores were evaluated. RESULTS The median [IQR] volume of intra-operative surgical bleeding was significantly less in the deep neuromuscular blockade group than in the moderate neuromuscular blockade group; 300 ml [200 to 494] vs. 415 ml [240 to 601]; difference: 117 ml (95% CI, 9 to 244; P = 0.044). The mean ± SD surgeon's satisfaction with the intra-operative surgical conditions was greater in the deep neuromuscular blockade group than in the moderate neuromuscular blockade group; 3.5 ± 1.0 vs. 2.9 ± 0.9 (P = 0.004). In intergroup comparisons of respiratory variables, peak inspiratory pressure was lower in the deep neuromuscular blockade group overall (P < 0.001). The median [IQR] postoperative pain score was lower in the deep neuromuscular blockade group than the moderate neuromuscular blockade group; 50 [36 to 60] vs. 60 [50 to 70], (P = 0.023). CONCLUSION Deep neuromuscular blockade reduced intra-operative surgical bleeding in patients undergoing spinal surgery. This may be related to greater relaxation in the back muscles and lower intra-operative peak inspiratory pressure when compared with moderate neuromuscular blockade. TRIAL REGISTRATION KCT0001264 (http://cris.nih.go.kr).

Postoperative residual neuromuscular blockade after reversal based on a qualitative peripheral nerve stimulator response: A randomised controlled trial BACKGROUND Incomplete recovery of neuromuscular blockade is a common postoperative adverse event in the postanaesthesia care unit. OBJECTIVE We examined and compared the incidence of residual neuromuscular blockade when the recommended dose of neostigmine or sugammadex was administered according to a qualitative nerve stimulator response. DESIGN A randomised controlled trial. SETTING A tertiary care hospital in South Korea from September 2017 to November 2017. PATIENTS Eighty patients aged between 18 and 69 years were included in this study. All were patients scheduled to undergo elective laparoscopic cholecystectomy and who had an American Society of Anaesthesiologists physical status of one or two were eligible. INTERVENTIONS Patients were allocated randomly to receive neostigmine or sugammadex at the end of surgery. The doses of the reversal agents were based on the response to peripheral nerve stimulation, which was discontinued after administration of the reversal agent. MAIN OUTCOME MEASURES The primary outcome was the incidence of postoperative residual neuromuscular blockade. The secondary outcomes were the incidences of symptoms or signs of residual neuromuscular blockade such as hypoxaemia, inability to maintain head-lift for 5 s and diplopia. RESULTS The incidence of residual neuromuscular blockade on arrival in the recovery room was 44.4% in the neostigmine group and 0% in the sugammadex group (P < 0.0001, relative risk = 1.80, 95% confidence interval 1.36 to 2.41). The incidences of adverse events in the recovery room were low and comparable between the groups. CONCLUSION The incidence of residual neuromuscular blockade on arrival in the recovery room was significantly higher in the neostigmine group than that in the sugammadex group. However, the incidence of adverse events was similar in the neostigmine and sugammadex groups. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03292965.

Spontaneous recovery of neuromuscular blockade is an independent risk factor for postoperative pulmonary complications after abdominal surgery: A secondary analysis BACKGROUND In intermediate-to-high-risk patients, major abdominal surgery is associated with a high incidence of postoperative complications, mainly pulmonary. Neuromuscular blocking drugs have been suggested as a contributing factor, but this remains unproven. OBJECTIVE To define the relationship of neuromuscular blockade management (reversal) with postoperative pulmonary complications (PPCs). DESIGN The individualised PeRioperative Open-lung approach Versus standard protectivE ventilation in abdominal surgery study was a prospective, multicentre, four-arm, randomised controlled trial. This is a secondary analysis of the data. SETTING Twenty-one teaching hospitals in Spain. The study was conducted between 2 January 2015, and 18 May 2016. PATIENTS Age more than 18 years with an intermediate-to-high risk for PPCs, scheduled for major abdominal surgery lasting more than 2 h. Exclusion criteria included pregnancy or breastfeeding, and moderate-to-severe organ diseases. INTERVENTIONS The mode of reversal of neuromuscular blockade determined two patient groups: pharmacological reversal versus spontaneous recovery. MAIN OUTCOME MEASURES The primary outcome was a composite of PPCs during the first 30 postoperative days. The association between categorical variables and PPCs within 30 days was studied. Univariate and multivariable logistic regression modelling and propensity score analyses were performed. RESULTS From the 923 patients included, 596 (64.6%) presented with PPCs within 30 days after surgery. Patients who developed these complications were older with a higher BMI, a lower pre-operative SpO2, a higher ASA physical status score and a higher incidence of arterial hypertension, diabetes mellitus or chronic obstructive pulmonary disease. Pharmacological neuromuscular blockade reversal was associated with a lower incidence of PPCs (odds ratio 0.62, 95% CI 0.47 to 0.82). CONCLUSION Spontaneous recovery of neuromuscular blockade was an independent risk factor for PPCs in patients with intermediate-to-high risk, undergoing abdominal surgery. We suggest this factor should be included in future studies on PPCs. TRIAL REGISTRATION clinicaltrials.gov identifier: NCT02158923.

The effect of intravenous magnesium on postoperative morphine consumption in noncardiac surgery: A systematic review and meta-analysis with trial sequential analysis BACKGROUND Several studies suggest that systemic magnesium reduces postoperative opioid consumption and the intensity of pain, but others report conflicting results. The efficacy and safety profile of intravenous magnesium in noncardiac surgery remain uncertain. OBJECTIVES The aim of this review was to investigate the effect of intravenous magnesium on the consumption of postoperative morphine in the first 24 h in adults undergoing noncardiac surgery. DESIGN Systematic review and meta-analysis with trial sequential analysis. DATA SOURCES MEDLINE, EMBASE, CENTRAL from their inception until January 2019. ELIGIBILITY CRITERIA All randomised clinical trials comparing intravenous magnesium versus placebo in noncardiac surgery were systematically searched in the databases. Observational studies, case reports, case series and nonsystematic reviews were excluded. RESULTS Fifty-one trials (n=3311) were included for quantitative meta-analysis. In comparison with placebo, postoperative morphine consumption at 24-h was significantly reduced in the magnesium group, with a mean difference [95% confidence interval (CI)] of −5.6 mg (−7.54 to −3.66, P < 0.001, I2 = 92%, level of evidence low). The trial sequential analysis for the effect of magnesium on postoperative morphine consumption was conclusive. Patients who received magnesium had a longer time to the first analgesia request [143 (103 to 183) min, P < 0.001, I2 = 99%, level of evidence low] and a lower incidence of shivering [0.26 (0.15 to 0.44), P < 0.001, I2 = 35%, level of evidence very low]. However, no significance differences were demonstrated in postoperative pain scores in the first 24 h (mean difference, 95% CI) −0.30 (−0.69 to 0.09, P = 0.13, I2 = 91%, level of evidence low), bradycardia (odds ratio, 95% CI) 1.13 (0.43 to 2.98, P = 0.80, I2 = 35%, level of evidence very low) and postoperative nausea and vomiting (odds ratio, 95% CI) 0.90 (0.67 to 1.22, P = 0.49, I2 = 25%, level of evidence moderate). CONCLUSION The current meta-analysis demonstrates that the use of intravenous magnesium as part of multimodal analgesia may reduce morphine consumption in the first 24 h after surgery and delay the time to the first request for analgesia in patients undergoing noncardiac surgery. However, the included studies were of low-quality with substantial heterogeneity. TRIAL REGISTRATION CRD42018086846.

Synergistic effect of the association between lidocaine and magnesium sulfate on peri-operative pain after mastectomy: A randomised, double-blind trial BACKGROUND Recently, the use of venous adjuvants, such as lidocaine and magnesium sulfate, has been gaining ground in multimodal analgesia. However, no study has evaluated the impact a combination of the two drugs. OBJECTIVES To evaluate the efficacy of venous adjuvants in reducing opioid consumption and pain scores after mastectomy. DESIGN Randomised, double-blind, parallel-group, noninferiority clinical trial with a 1 : 1 : 1 : 1 allocation ratio. SETTING Hospital de Base do Distrito Federal, Brasilia, Federal District, Brazil from November 2014 to December 2017. PATIENTS One-hundred and ninety-eight patients were electively scheduled for mastectomy. Seventy-eight were excluded. INTERVENTIONS Intra-operative infusions of remifentanil (0.1 μg kg−1 min−1), lidocaine (3 mg kg−1 h−1), magnesium sulfate (50 mg kg−1 + 15 mg kg−1 h−1) or lidocaine with magnesium sulfate were used. All patients received standard general anaesthesia. MAIN OUTCOME MEASURES Peri-operative opioid consumption and pain scores. RESULTS The patients who received both lidocaine and magnesium sulfate group (n=30) consumed less alfentanil during surgery (P < 0.001) and less dipyrone (P < 0.001) and morphine (P < 0.001) in the postoperative period. Only two patients (6.7%) in the lidocaine and magnesium sulfate group needed morphine (P < 0.001). These requirements were significantly lower when compared with patients who received remifentanil (n=30; 76.6%) and magnesium sulfate (n=30; 70%; odds ratio 46.0, 95% confidence interval 8.69 to 243.25, P < 0.001, and odds ratio 32.66, 95% confidence interval 6.37 to 167.27, P < 0.001, respectively). The patients of the lidocaine and magnesium sulfate group had lower pain scores in the first 24 h postoperatively using the numerical rating scale and verbal rating scale at discharge from the postanaesthesia care unit (P < 0.001), after 12 h (P < 0.001) and after 24 h (P < 0.001) when compared with the other three groups. CONCLUSION Our findings suggest a synergistic effect of the use of both lidocaine and magnesium in peri-operative pain. This may be another potential strategy in the multimodal analgesia regimen. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02309879.

Data-science-based subgroup analysis of persistent pain during 3 years after breast cancer surgery: A prospective cohort study BACKGROUND Persistent pain extending beyond 6 months after breast cancer surgery when adjuvant therapies have ended is a recognised phenomenon. The evolution of postsurgery pain is therefore of interest for future patient management in terms of possible prognoses for distinct groups of patients to enable better patient information. OBJECTIVE(S) An analysis aimed to identify subgroups of patients who share similar time courses of postoperative persistent pain. DESIGN Prospective cohort study. SETTING Helsinki University Hospital, Finland, between 2006 and 2010. PATIENTS A total of 763 women treated for breast cancer at the Helsinki University Hospital. INTERVENTIONS Employing a data science approach in a nonredundant reanalysis of data published previously, pain ratings acquired at 6, 12, 24 and 36 months after breast cancer surgery, were analysed for a group structure of the temporal courses of pain. Unsupervised automated evolutionary (genetic) algorithms were used for patient cluster detection in the pain ratings and for Gaussian mixture modelling of the slopes of the linear relationship between pain ratings and acquisition times. MAIN OUTCOME MEASURES Clusters or groups of patients sharing patterns in the time courses of pain between 6 and 36 months after breast cancer surgery. RESULTS Three groups of patients with distinct time courses of pain were identified as the best solutions for both clustering of the pain ratings and multimodal modelling of the slopes of their temporal trends. In two clusters/groups, pain decreased or remained stable and the two approaches suggested/identified similar subgroups representing 80/763 and 86/763 of the patients, respectively, in whom rather high pain levels tended to further increase over time. CONCLUSION In the majority of patients, pain after breast cancer surgery decreased rapidly and disappeared or the intensity decreased over 3 years. However, in about a tenth of patients, moderate-to-severe pain tended to increase during the 3-year follow-up.